A leading cause of nosocomial infections is the Gram-positive bacteria Enterococcus species. Due to the increasing number of untreatable, persistent E. faecalis and E. faecium infections, there is an immediate surge to develop novel and alternate therapies dealing with E. faecalis and E. faecium infections. The goal of this exploratory grant is to develop a radical approach to identify novel classes of antimicrobials. Our previous work has demonstrated that plants could be used as a facile and inexpensive model to characterize E. faecalis infections. We are proposing the development of a screen for novel antimicrobial compounds by co-culturing E. faecalis and E. faecium with a variety of plant species. This screen would utilize the plant roots ability to sense and respond to the bacteria through specific elicitation of compounds and infectivity in plant would serve as an indicator. Plant not infected by the bacteria are likely producing and exuding antimicrobial compounds. We are confident that this system could easily be adapted for use with E. faecalis and E. faecium. We hypothesize that since E. faecalis and E. faecium is capable of infecting plants under laboratory conditions, there is an exciting possibility that some plant species that are not infected with E. faecalis and E. faecium exude antimicrobial compounds. The specific aims are Aim 1: To apply a simple root screening method to test E. faecalis and E. faecium pathogenicity. Identify plant species that resist infection by E. faecalis and E. faecium and collect their root exudates. Determine bioactivity of root exudates in antimicrobial assays. Aim 2: To identify and chemically characterize compound(s) from the root exudates of resistant and tolerant plant species that exhibit antimicrobial properties against E. faecalis and E. faecium. It is expected that these novel efforts will lead to the development of new therapeutics for treatment against E. faecalis and E. faecium infections either by a stand-alone drug or by enhancing the effectiveness of existing drug therapies. PUBLIC HEALTH RELEVANCE: The research outlined in this grant proposes the development of an alternative therapeutic approach to treat Enterococcus infections. It is expected that these novel efforts will lead to the development of new therapeutics for treatment of E. faecalis and E. faecium infections either by a stand-alone drug or by augmenting the effectiveness of existing drug therapies.